Head and Neck Pathol (2018) 12:562–566
DOI 10.1007/s12105-017-0849-3
SINE QUA NON RADIOLOGY-PATHOLOGY
Adenoid Cystic Carcinoma of the Oral Cavity:
Radiology–Pathology Correlation
Imran Uraizee1 · Nicole A. Cipriani1 · Daniel T. Ginat2
Received: 8 August 2017 / Accepted: 28 August 2017 / Published online: 6 September 2017
© Springer Science+Business Media, LLC 2017
Abstract Adenoid cystic carcinoma in the oral cavity is
an uncommon salivary gland malignancy that has a pro-
pensity for perineural spread. A high-grade variant is evi-
denced by an abundance of pleomorphic cells, loss of the
classic biphasic epithelial-myoepithelial growth pattern, and
comedonecrosis, as well as elevated Ki-67. CT and MRI can
both be useful for demonstrating the extent of invasion in
oral cavity-associated adenoid cystic carcinoma, which can
attain the inferior alveolar nerve for perineural spread by
direct invasion through the mandible. Reflecting the aggres-
sive nature of this high-grade malignancy, 18FDG-PET can
demonstrate hypermetabolism and can be useful for staging.
These features are exemplified in this sine qua non radiol-
ogy–pathology correlation article.
Keywords Adenoid cystic carcinoma · Pathology ·
Radiology
History
A 59-year-old male with a 25 pack-year smoking history
presented with a lump under the left tongue, dysphagia, and
left chin numbness. The patient had undergone recent dental
extractions, and it was initially believed by his dentist to be
an abscess. The patient was subsequently referred to otolar-
yngology at our institution when the lesion started bleeding
* Daniel T. Ginat
dtg1@uchicago.edu
1
Department of Pathology, University of Chicago, Chicago,
IL, USA
2
Department of Radiology, University of Chicago, 5841 S
Maryland Avenue, Chicago, IL 60637, USA
13
Vol:.(1234567890)
3 months later, during which time the patient experienced
30 pounds of weight loss. The patient did not have additional
significant past medical history.
Radiological Features
CT with contrast was performed, which showed an infil-
trative mass centered in the left sublingual space (arrow)
with invasion into the left mandibular body (Fig. 1). The
degree of mandibular bone marrow invasion was more con-
spicuous on MRI, which was obtained shortly after the CT
(Fig. 2). Furthermore, the mass was markedly hypermeta-
bolic on 18FDG-PET/CT, which otherwise did not demon-
strate metastases. The differential considerations based on
the imaging include salivary gland malignancy, squamous
cell carcinoma, and sarcoma.
Diagnosis and Treatment
The patient underwent left hemi-mandibulectomy, hemi-
glossectomy, and floor of mouth resection with bilateral
neck dissection. The gross resection specimen showed an
unencapsulated, ill-defined, firm, tan-white mass measur-
ing 5.7 cm in greatest dimension, centered in the floor of
mouth with infiltration into adjacent mandible, lingual skel-
etal muscle, and fibroadipose tissue (Fig. 3). There was also
direct extension of the tumor into an adjacent lymph node.
Hematoxylin and eosin-stained sections revealed two dis-
tinct areas in the tumor: an area of nested, duct-like growth
containing cells with high nuclear:cytoplasmic ratios, oval to
angulated nuclei with coarse chromatin, and variably promi-
nent nucleoli; and an adjacent area of solid sheet-like growth
with pleomorphic nuclei and increased mitoses (Fig. 4). In
Head and Neck Pathol (2018) 12:562–566 563

Fig. 1  Coronal soft tissue (a) and bone (b) window post-contrast CT head), with obliteration of the inferior alveolar canal, which attests to
images show an infiltrative mass centered in the left sublingual space the aggressive behavior of a malignant neoplasm
(arrow) with direct invasion into the left mandibular body (arrow-

Fig. 3  The gross specimen reveals an ill-defined, firm, tan-white

mass centered on the floor of mouth with invasion of lingual skeletal
Fig. 2  Coronal T1-weighted MRI shows an infiltrative mass (arrow) muscle and the mandible (asterisk), without distinguishable residual
in the left oral cavity with invasion of the surrounding musculature normal sublingual gland
and extension into the left mandibular bone marrow, where it envel-
ops the left inferior alveolar nerve, which is consequently insepara-
ble from the tumor. By comparison, the intact right inferior alveolar
nerve is visible in cross-section (arrowhead)

13
564
Fig. 4  Hematoxylin and eosin-stained sections show two distinct
areas: a relatively well-differentiated carcinoma with nested, duct-
like growth containing cells with high nuclear:cytoplasmic ratios,
oval nuclei with coarse chromatin, and variably prominent nucleoli
Fig. 5  Low power hematoxylin and eosin-stained sections show variably-sized cords and nests of cells that infiltrate into skeletal muscle (a) and
bone with perineural invasion of the inferior alveolar nerve (b)
addition, variably-sized cords and nests of cells infiltrated
into skeletal muscle and bone with perineural invasion
(Fig. 5). Immunostains demonstrated p40, p63, and CK5/6
positive myoepithelial cells at the periphery of the nests and
c-kit (CD117) positive epithelial cells at the center of the
nests. Overall, these features were consistent with a high-
grade variant of adenoid cystic carcinoma.
The patient received seven cycles of TFHX (paclitaxel,
infusional 5-fluorouracil, hydroxyurea, and twice-daily
radiation therapy administered every other week) with no
evidence of recurrence at 6 months after resection.
13
Head and Neck Pathol (2018) 12:562–566
(a, left side); and a more poorly-differentiated carcinoma with solid,
sheet-like growth with pleomorphic nuclei and increased mitoses (a,
right side). Occasional tumor necrosis was present in areas of solid-
to-nested growth (b)
Discussion
Adenoid cystic carcinoma is a malignant neoplasm that pre-
dominantly originates from the submandibular, sublingual,
and minor salivary glands and is comprised of epithelial
and myoepithelial cells organized in tubular, cribriform,
solid, or combined architectural forms [1]. It is a relatively
uncommon neoplasm, representing about 1% of all malig-
nant tumors in the head and neck region and is the fourth
most common malignant salivary gland tumor accounting
for 10% of all such tumors [2, 3]. Adenoid cystic carcinoma
is slightly more prevalent in females than males and occurs
Head and Neck Pathol (2018) 12:562–566
most commonly during the fifth and sixth decades of life
[4, 5].
Salivary gland tumors are usually best depicted on MRI.
In particular, involvement of cranial nerves and tumoral
infiltration around the nerves and osseous structures is opti-
mally assessed via non-contrast T1-weighted and contrast-
enhanced, fat-suppressed T1-weighted MR sequences [6].
Perineural spread typically appears as enlargement and
abnormal enhancement of the affected nerve and widening
or obliteration of the nerve canal. Since adenoid cystic car-
cinoma of the oral cavity can attain, engulf, and infiltrate
the inferior alveolar nerve by first eroding through the man-
dibular cortex and infiltrating through the bone marrow, CT
can be complementary to MRI, as demonstrated in this case.
In general, 18FDG-PET is considered complementary and
sometimes superior to anatomical imaging modalities for
staging and restaging of salivary gland malignancies and
PET often has a positive impact on clinical management for
such cases [7]. High-grade salivary gland malignancies tend
to be more hypermetabolic than low- and intermediate-grade
malignancies, as exemplified in this case of adenoid cystic
carcinoma [8]. However, adenoid cystic carcinomas often do
not have significant activity on 18FDG-PET, perhaps due to
their slow growth [9]. The aggressive nature of the adenoid
cystic carcinoma in this case may account for the hyperme-
tabolism on 18FDG-PET.
Grossly, the adenoid cystic carcinoma tends to be poorly
circumscribed, unencapsulated, and firm with a white to
gray-white cut surface and significant variability in size [5].
Hemorrhage and necrosis are not common gross features,
but if observed, should raise concern for a high-grade variant
[5]. Histologically, the tumor is heterogeneous with varying
combinations of the three distinct architectural patterns [1,
5]. The tumor cells are usually quite uniform in appearance
with scant clear to slightly eosinophilic cytoplasm and bland,
oval to sharply angulated basophilic nuclei with coarse chro-
matin. The tubular pattern is the least common type and low-
est grade with small nests of ductal cells surrounded com-
pletely by a second myoepithelial cell layer in a background
of eosinophilic hyalinized stroma [5]. The cribriform pattern
is most common and is comprised of invasive islands of
basaloid cells with many cystlike spaces, referred to as pseu-
docysts, forming a “Swiss-cheese” or “sieve-like” pattern [1,
2, 5]. The solid pattern demonstrates large islands and cords
of carcinoma with areas of necrosis, increased mitotic activ-
ity, and perineural spread [5]. A high-grade variant must be
identified in the setting of conventional adenoid cystic car-
cinoma and is evidenced by increasingly pleomorphic cells,
loss of the classic biphasic epithelial-myoepithelial growth
pattern, and comedonecrosis [5].
Immunohistochemical stains for smooth muscle actin,
S100, p40, p63 demonstrate positivity in myoepithelial
cells of adenoid cystic carcinoma [5, 10]. Adenoid cystic
565
carcinoma also demonstrates strong positive staining
for c-kit (CD117) in tumor cells regardless of pattern or
grade [10–12]. Increased cellular proliferation as assessed
by Ki-67 has also been described in high-grade solid-type
adenoid cystic carcinoma and been shown to correlate with
a worse prognosis [13]. The histologic differential diagnosis
includes polymorphous adenocarcinoma, carcinoma ex pleo-
morphic adenoma, and basal cell adenocarcinoma.
Many adenoid cystic carcinomas are characterized by
recently described recurrent chromosomal rearrangements,
including t(6;9) [14, 15]. Persson et al. revealed that this
translocation resulted in the fusion of two transcription fac-
tors, MYB-NFIB, which subsequently spurred studies on the
role of MYB (myeloblastosis) overexpression in the patho-
genesis of ACC [14, 16]. While a significant proportion of
adenoid cystic carcinomas do not harbor this specific chro-
mosomal aberration, the identification of the MYBL1-NFIB
fusion product resulting from t(8;9) translocations suggested
that overexpression of transcription factors from the family
of MYB genes may play a key role in adenoid cystic carci-
noma tumorigenesis [17, 18]. The exact biological sequence
of events that drives the growth of adenoid cystic carcinoma
still remains unclear. However, the emerging model sug-
gests transformation of a low-grade neoplasm resulting from
altered regulation of the MYB locus leads to subsequent
growth and acquisition of additional genetic hits [15]. Novel
therapies targeting the MYB protein may show more prom-
ise as our understanding of this sequence improves.
The likelihood of lymph node metastases increases by
5–10 fold in patients with high-grade variants of adenoid
cystic carcinoma, occurring in 43–57% of patients with
tumors showing these histologic features [19]. Thus, stand-
ard neck dissection is considered mandatory in patients with
such tumors.
Acknowledgements We are grateful for support received from the
University of Chicago Office of Faculty Affairs through the Faculty
Initiatives Fund for our Head and Neck Radiology–Pathology Trainee
Conference, during which this case was presented.
Compliance with Ethical Standards
Conflict of interest The authors declare that they have no conflict
of interest.
References
1. Azumi N, Battifora H. The cellular composition of adenoid
cystic carcinoma. An immunohistochemical study. Cancer.
1987;60:1589–98.
2. Spiro RH, Huvos AG, Strong EW. Adenoid cystic carcinoma of
salivary origin. A clinicopathologic study of 242 cases. Am J
Surg. 1974;128:512–20.
13
566
3. Dillon PM, Chakraborty S, Moskaluk CA, et al. Adenoid cystic
carcinoma: a review of recent advances, molecular targets, and
clinical trials. Head Neck. 2016;38:620–7.
4. Li N, Xu L, Zhao H, et al. A comparison of the demographics,
clinical features, and survival of patients with adenoid cystic car-
cinoma of major and minor salivary glands versus less common
sites within the Surveillance, Epidemiology, and End Results reg-
istry. Cancer. 2012;118:3945–53.
5. Jaso J, Malhotra R. Adenoid cystic carcinoma. Arch Pathol Lab
Med. 2011;135:511–5.
6. Yousem DM, Kraut MA, Chalian AA. Major salivary gland imag-
ing. Radiology. 2000;216:19–29.
7. Bertagna F, Nicolai P, Maroldi R, Mattavelli D, Bertoli M, Giub-
bini R, Lombardi D, Treglia G. Diagnostic role of (18)F-FDG-
PET or PET/CT in salivary gland tumors: a systematic review.
Rev Esp Med Nucl Imagen Mol. 2015;34:295–302.
8. Roh JL, Ryu CH, Choi SH, et al. Clinical utility of 18 F-FDG
PET for patients with salivary gland malignancies. J Nucl Med.
2007;48:240–6.
9. Purohit BS, Ailianou A, Dulguerov N, Becker CD, Ratib O,
Becker M. FDG-PET/CT pitfalls in oncological head and neck
imaging. Insights Imaging. 2014;5:585–602.
10. Rooper L, Sharma R, Bishop JA. Polymorphous low grade ade-
nocarcinoma has a consistent p63+/p40- immunophenotype that
helps distinguish it from adenoid cystic carcinoma and cellular
pleomorphic adenoma. Head Neck. 2015;9:79–84.
11. Penner CR, Folpe AL, Budnick SD. C-kit expression distinguishes
salivary gland adenoid cystic carcinoma from polymorphous low-
grade adenocarcinoma. Mod Pathol. 2002;15:687–91.
13
Head and Neck Pathol (2018) 12:562–566
12. Vila L, Liu H, Al-Quran S, et al. Identification of c-kit gene muta-
tions in primary adenoid cystic carcinoma of the salivary gland.
Mod Pathol. 2009;22:1296–302.
13. Spaak LN, Dardick I, Ledin T. Adenoid cystic carcinoma: use
of cell proliferation, bcl-2 expression histologic grade, and
clinical stage as predictors of clinical outcome. Head Neck.
2000;22:489–97.
14. Wysocki PT, Izumchenko E, Meir J, et al. Adenoid cystic carci-
noma: emerging role of translocations and gene fusions. Onco-
target. 2016;7:66239–54.
15. Moskaluk CA. Adenoid cystic carcinoma: clinical and molecular
features. Head Neck. 2013;7:17–22.
16. Persson M, Andren Y, Mark J, et al. Recurrent fusion of MYB and
NFIB transcription factor genes in carcinomas of the breast and
head and neck. Proc Natl Acad Sci USA. 2009;106:18740–4.
17. Mitani Y, Liu B, Rao P, et al. Novel MYBL1 gene rearrangements
with recurrent MYBL1-NFIB fusions in salivary adenoid cystic
carcinomas lacking t(6;9) translocations. Clin Cancer Res. 2015.
18. Brayer KJ, Frerich CA, Kang H, et al. Recurrent fusions in MYB
and MYBL1 define a common transcription factor-driven onco-
genic pathway in salivary gland adenoid cystic carcinoma. Cancer
Discov. 2015.
19. Hellquist H, Skálová A, Barnes L, et al. Cervical lymph node
metastasis in high-grade transformation of head and neck adenoid
cystic carcinoma: a collective international review. Adv Ther.
2016;33:357–68.